New Glutamate Modulator Shows Promise in Treating Schizophrenia-Related Dysfunction

Recent preclinical research published in Neuropsychopharmacology has highlighted the potential of the glutamate modulator, evenamide, as a groundbreaking treatment for schizophrenia. Conducted by scientists at the University of Pittsburgh, the study used an animal model known as methylazoxymethanol acetate (MAM), which simulates various aspects of the neurodevelopmental disorder. The findings demonstrate that evenamide, produced by Newron Pharmaceuticals, effectively reduces hippocampal hyperexcitability and normalizes the activity of dopaminergic neurons, which are often dysregulated in schizophrenia.

Schizophrenia affects approximately 1% of the global population and is characterized by a spectrum of symptoms including positive (hallucinations, delusions), negative (social withdrawal, apathy), and cognitive impairments. Current antipsychotic drugs primarily target positive symptoms by blocking dopamine D2 receptors, but they fall short in addressing cognitive deficits and negative symptoms.

The study reveals that evenamide specifically targets hyperactive neurons in the hippocampus, a brain region known to exhibit hyperexcitability in schizophrenia. Unlike traditional treatments, it acts by inhibiting voltage-gated sodium channels, which results in decreased hippocampal hyperactivity. The research also indicates that a single dose of evenamide has lasting effects, potentially impacting neuronal plasticity, and reduces excessive glutamate activity associated with NMDA receptor hypofunction.

Lead researcher Daniela L. Uliana explained that their experiments demonstrated that acute treatment with evenamide reversed hyperdopaminergic activity, social deficits, and recognition memory impairments in the animal model. This suggests that the drug could not only mitigate positive symptoms but also improve cognitive and social dysfunctions—areas where current therapies are limited.

Moreover, the research findings support the notion that evenamide offers a novel mechanism of action by targeting hippocampal hyperexcitability without the side effects typically associated with D2 receptor blockade. Dr. Anthony A. Grace, senior study author, emphasized that this represents a significant advancement in schizophrenia treatment because it could provide a comprehensive approach to managing multiple symptom domains.

In clinical settings, these promising preclinical results are bolstered by ongoing trials. Ravi Anand, Chief Medical Officer at Newron Pharmaceuticals, highlighted that prior Phase II and III trials in patients with treatment-resistant schizophrenia have shown that evenamide can produce sustained symptom improvements even a year after treatment initiation. The drug’s ability to enhance cognitive function and social behaviors could markedly improve patient outcomes.

This emerging evidence positions evenamide as a potential game-changer in the landscape of schizophrenia therapy, addressing not only the dopaminergic imbalance but also underlying neurophysiological abnormalities that contribute to the disorder’s complexity.